Abstract
Specialized pro-resolving lipid mediators regulate the resolution of acute inflammation. They are formed by enzymatic oxygenation of polyunsaturated fatty acids and are divided into families including lipoxins, resolvins, protectins, and maresins. Resolvin D1 (RvD1), produced by docosahexaenoic acid, exerts anti-inflammatory and pro-resolving activities. This research aimed to investigate the implication of seminal RvD1 in human infertility. Infertile patients (n° 67) were grouped based on pathological reproductive conditions as idiopathic infertility, varicocele, and leukocytospermia; the fourth group was composed of fertile men (n° 18). Sperm characteristics were evaluated by light microscopy (WHO guidelines) and by transmission electron microscopy (TEM). The seminal levels of RvD1 and F2-isoprostane (F2-IsoPs) were dosed. In twenty men (6 fertile men, 8 with varicocele, 6 with leukocytospermia) seminal phospholipase A2, iron, cholesterol, transferrin, estradiol, ferritin, testosterone, and sperm membrane fatty acids were detected. The results indicated that: (i) RvD1 amount was positively correlated with F2-IsoPs and reduced sperm quality; (ii) RvD1 levels were significantly higher in patients with leukocytospermia, varicocele, and idiopathic infertility compared to fertile men; (iii) RvD1 increased along with other markers of oxidative stress and inflammation as fatty acids content and clinical biomarkers. This study suggests a panel of inflammatory markers and lipid mediators for a diagnosis of inflammatory status and a subsequent appropriate therapeutic approach.
Highlights
As a peculiar evolution of inflammation, which is a humans’ defense mechanism against pathological agents, acute inflammation starts rapidly once biological damage has occurred, resolves in a few days, and is regulated by chemical mediators, such as enzymatic metabolites of arachidonic acid (AA) [1,2,3]
Sperm concentration, progressive motility, normal morphology, and vitality were evaluated in seminal samples of 85 individuals [24]; sperm ultrastructure was deeply investigated by transmission electron microscopy (TEM)
In this study a decrease in Resolvin D1 (RvD1), FERR levels, and n-6/n-3 ratio as well as an increase in docosahexaenoic acid (DHA) and total n-3 contents detected in the fertile group strongly suggest RvD1 as indicators of a pathological seminal condition (Figure 6)
Summary
As a peculiar evolution of inflammation, which is a humans’ defense mechanism against pathological agents, acute inflammation starts rapidly once biological damage has occurred, resolves in a few days, and is regulated by chemical mediators, such as enzymatic metabolites of arachidonic acid (AA) [1,2,3]. Specialized pro-resolving lipid mediators (SPMs) are reported to be able to regulate the resolution of acute inflammation that should be considered as an active process moved by specific regulatory molecules (i.e., SPMs) [5]. SPMs are formed by enzymatic oxygenation of polyunsaturated fatty acids (PUFAs) and are divided into families including lipoxins, resolvins, protectins, and maresins [6,7]. The switch from the initiation to the resolution phase of acute inflammatory response is crucial
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